• Clinical science

Oral anticoagulants


Anticoagulants are used for treating and preventing embolic events. The most common oral anticoagulatory agents are vitamin K antagonists such as warfarin (Coumadin®) and phenprocoumon. Non-vitamin K antagonist oral anticoagulants (NOACs) like dabigatran and rivaroxaban have also gained popularity in recent years. Vitamin K antagonists inhibit the enzyme vitamin K epoxide reductase, thereby blocking hepatic synthesis of the active, reduced form of vitamin K (needed for carboxylation of coagulation factors II, VII, IX, and X, protein C, protein S). This effect can last for several days, which complicates exact dosing and makes regular monitoring necessary. Vitamin K antagonists are also metabolized by C-P450 (CYP) enzymes and therefore interact with a broad range of foods and drugs. NOACs act selectively via inhibition of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban). Because of their comparatively short half-life and fewer interactions, NOACs are easier to control and administer than warfarin and do not require regular monitoring to ensure their efficacy and safety. There are no established tests for monitoring overdosing since the usual coagulation studies (aPTT, factor Xa activity) can yield false results. For all substances, it is important to consider the dose-dependent risk of bleeding, especially when combining different substances that affect hemostasis (e.g., aspirin, clopidogrel, ticagrelor).


Overview of commonly used oral anticoagulants

Substances Mechanism of action
Advantages Disadvantages
Vitamin K antagonists (coumarins)



  • Inhibit hepatic vitamin K epoxide reductase↓ hepatic synthesis (recycling) of the active, reduced form of vitamin Kγ-carboxylation of glutamate residues on coagulation factors II, VII, IX, and X
  • Well-known effects and side effects
  • Low costs
  • In cases of life-threatening bleeding: direct reversal by replacement (e.g., prothrombin complex concentrate, FFP) or indirect/delayed reversal by increasing production of coagulation factors (e.g., vitamin K)
Non-vitamin K antagonist oral anticoagulants
Direct oral thrombin inhibitors


  • Easily manageable (similar to heparins) when administered orally
    • Regular monitoring of coagulation parameters not required → improved patient compliance
  • Antidotes available in the case of life-threatening bleeding
  • Costly
  • Limited clinical experience with these drugs
  • Not recommended, and partially contraindicated, in patients with artificial cardiac valves
  • Not suited for patients with valvular atrial fibrillation
Direct oral factor Xa inhibitors




  • Selective and direct inhibition of factor Xa
General notes regarding oral anticoagulation
Indications for all oral anticoagulants

Expected laboratory changes

  • Warfarin: increased PT/INR, no change to PTT or TT (routinely monitored)
  • Direct thrombin inhibitors: prolonged TT, no change to PTT or PT (not routinely monitored)
  • Direct factor Xa inhibitors: prolonged PT and PTT, unchanged TT (not routinely monitored)

The most important side effect of all oral anticoagulants is a dose-dependent increase in bleeding risk!


Side effects


Individuals with protein C deficiency are at a higher risk of developing warfarin necrosis!

Direct factor Xa inhibitors and direct thrombin inhibitors

  • Dose-dependent increased risk of bleeding
    • Interventional steps to stop the bleeding
    • If life-threatening bleeding occurs, administer PCC
    • Antifibrinolytic agents (e.g., tranexamic acid)
    • Oral activated charcoal; reduces absorption if anticoagulants were ingested in the past couple of hours.
    • Apixaban and rivaroxaban: andexanet alfa (recombinant modified factor Xa protein)
    • Dabigatran: idarucizumab (monoclonal antibody)


We list the most important adverse effects. The selection is not exhaustive.





Direct thrombin inhibitors


Direct factor Xa inhibitors






  • General contraindications
    • Coagulopathies; hepatic dysfunction with impaired hepatic production of coagulation factors
    • Acute bleeding
    • Suspected vascular lesions, increased risk of severe bleeding
    • Severe renal insufficiency
    • Concurrent administration of several anticoagulants
    • Pregnancy and breastfeeding
      • Warfarin crosses the placenta, causing teratogenicity and fetal bleeding
      • Side effects of NOACs during pregnancy and breastfeeding are unknown. Therefore, they are currently not recommended.
  • Specific contraindications


We list the most important contraindications. The selection is not exhaustive.


Warfarin interactions

Warfarin is metabolized by cytochrome P450 (CYP) enzymes. Its effects can be significantly impacted by a variety of interactions; for this reason, warfarin serum levels should be monitored regularly.

P450 inducers: warfarin levels (Chronic Alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs): C - Chronic alcohol use, S - St. John's wort, P - Phenytoin, P - Phenobarbital, N - Nevirapine, R - Rifampin, G - Griseofulvin, C - Carbamazepine

P450 inhibitors can be remembered with “sickfaces.com group”: S - Sulfonamides, I - Isoniazid, C - Cimetidine, K - Ketoconazole, F - Fluconazole , A - Alcohol (binge drinking), C - Ciprofloxacin, E - Erythromycin, S - Sodium valproate, C - Chloramphenicol, O - Omeprazole, M - Metronidazole, G - Grapefruit juice

Guidelines & therapy recommendations

  • Preoperative bridging therapy
    1. Stop coumarin administration 5–6 days before surgery.
    2. Administer a therapeutic dose of the bridging drug 3 days before surgery; , with the last dose administered 24 hours before the procedure.
    3. Resume the bridging drug and warfarin after surgery; ; administer the bridging drug for 4–6 days post-surgery.